J Letchford Lec 6 Tuberculosis Flashcards
Tuberculosis is often caused by M_______ T______.
Mycobacterium tuberculosis
Tuberculosis is a major opportunistic infection in ____ patients.
It is often called a la__ infection
AIDS
Latent
Tuberculosis is often caused by M_____ T______.
This is a slow growing b______.
It is an a____ fast bacteria.
It’s cell wall is rich in lipids
It is very hydro____ and resistant to drying
What will happen in a gram stain?
Why?
Mycobacterium Tuberculosis
Bacillus
Acid fast bacteria
Will not show up in gram stain as it’s fatty acids are resistant to gram stain and antibiotics.
M.tuberculosis complex:
M.tuberculosis, M.b____
M.africanum, M.m____
M.tuberculosis, M.bovis
M.africanum, M.microti
Primary tuberculosis:
Stage 1:
- B____ inhaled in droplets (need close contact for prolonged period of time)
- _______ by macrophages
- Macrophages do not destroy the b_____
Bacilli
Phagocytosed
Bacilli
Primary tuberculosis
Stage 2:
- M.TB multiplies inside _______ for 7-21 days
- ______ burst
- Incoming macrophages _______ released M.TB
Macrophages
Macrophages
Phagocytose
Primary tuberculosis
Stage 3:
- Cell mediated response initiated
- Tu____ formed that contain the bacilli in a collagen layer
Tubercules
Tuberculosis infections can be…
1) C______
2) Remain as a l_____ _____
3) Progress
Cleared Latent infection (most bacillus killed off in tubercles but some can remain dormant)
Primary tuberculosis
Stage 4:
- Bacteria multiply inside _____ if not controlled by the immune system and t______ rupture (uncontrolled lysis)
- Enzymes are released which destroy local tissues and cause l____
- This can be pulmonary TB (in lungs)
- Extra pulmonary TB (if into blood stream e.g immunocomp)
Macrophages
Tubercules
Lesions
What are 5 symptoms of TB?
1) Cough (prolonged and productive)
2) Afternoon fever
3) Weight loss
4) Blood stained sputum
5) Night sweats
(inability to thrive in children)
Diagnosis of Active TB:
Clinical exam
Chest x-ray (white l_____ replace alveoli with ____ _____)
Sputum test; smears and/or cultures:
Visualise TB bateria in sputum by staining and microscopy
Culture bacteria (see if strain is _____)
Lesions
Scar tissue (poor gas exchange)
Resistant
Diagnosis of latent TB:
_______ skin test:
______ injected s.c into forearm
POSITIVE: skin lesion bigger than 10mm diameter after 48 - 72hr
Molecular assays:
- Expert MTB/RIF assay (PCR amplifie bacterial genes to detect presence of bacillus)
- In___ ____ tests
Tuberculin skin test
Tuberculin injected S.C into forearm
Interferon gamma tests
Screening for TB on entry to UK:
- Compulsory for those travelling from country where TB common if want to stay in UK for more than _ months.
- Need BEFORE apply for ____
- Chest x-ray
- _____ test
6 months
VISA
Sputum-test
Prevention of TB - immunisation
\_\_\_ vaccine (up to 2005) Given to \_\_\_ \_\_\_\_ groups
BCG
High risk
Main criteria for anti-TB drugs:
- _______ activity (as bac divide in _____)
- Combination therapies (to reduce _____)
- Prolonged therapy with min SE’s and low toxicity
_ first line anti-TB drugs used as combination
Intracellular activity (as bacteria divides in macrophages)
To reduce resistance
4 first line anti-TB used in combination
1st line anti-TB drug: R______ (inhibit ___ polymerase)
- Bacteri____
- Orally absorbed
- Abs decreased by food
SE’s:
- ____ damage
- Hypersensitivity
- ____ activity of other drugs
- ____ ____ in body fluids
Rifampicin
Bactericidal
Liver damage
Reduce activity
Red colour (breast milk, tears)
1st line anti-TB drug: I_______
- Bacter_____ or bacteri_____ pro-drug
- Decrease synth _____ acid (lipid component cell wall)
PK: IV, IM, ORAL
Distributed in CSF
Metab in ____, excreted by ____
SE's: Hypersensitivity Peripheral neuropathy Liver toxicity (LFT) Reduced efficacy of \_\_\_\_\_ \_\_\_\_\_ \_\_\_\_\_
Isoniazid
Bactericidal or bacteriostatic pro drug
Decrease synthesis of mycolic acid (lipid component of cell wall)
Liver
Kidneys
Hormonal birth control
1st line anti-TB drug: P_______
- Bacteri____, antibiotic prodrug
- Decrease synthesis of m____ acid/ damages bacterial membrane
PK: oral, well abs
Metab by ____, excrete by ____
SE’s:
- Joint pain
- _____ damage
- Hypersensitivity
Pyrazinamide
Bactericidal
Mycolic acid (in lipid cell wall)
Liver, Kindeys
Liver damage
1st line anti-TB drug: E______
- Bacteri____
- Increase _____ __ ___ ___
PK:
Oral, well absorbed, well distributed
50% excreted unchanged
SE’s:
_____ neuritis: reversible (colour blindness and impaired)
Joint pain
Ethambutol
Bacteriostatic
Increase permeability of cell wall
Optic neuritis
Which 1st line drugs do the following?
1) Inhibit cell wall synthesis
2) Inhibit cell wall synthesis
3) Inhibit RNA synthesis
4) Disrupts plasma membrane and disrupts energy metabolism
Rifampicin, Ethambutol, Pyrazinamide, Isoniazid
Isoniazid
Ethambutol
Rifampicin
Pyrazinamide
2nd line anti-TB drugs:
Aminoglycosides: S_____, Capreomycin
C______: (neurological SE’s)
Quinolone: Ci_____
Macrolide: Az_____
Streptomycin
Cycloserine
Ciprofloxacin
Azithromycin
Treatment of TB:
Active TB: RIPE
- R______ and I______ for _ to _ months
- P______ for _ months and E______
Latent TB: Treat specific patient groups - I\_\_\_\_\_ 6 months OR - R\_\_\_\_\_ and I\_\_\_\_\_\_ 3 months
Rifampicin and Isoniazid for 6-9 months
Pyrazinamide for 2 months and Ethambutol
Isoniazid 6 months
Rifampicin and Isoniazid 3 months
TB and resistance:
- Results from poorly managed TB care
MDR-TB - Strains resistant to _ or more of first line drugs
XDR-TB - Strains resistant to _ or more of first line drugs AND _ or more of second line drugs
2 or more
2 or more
3 or more
